The development of new and novel synthetic approaches to three different families of antitumor agents is proposed. In this way, systematic structural variation of this class of compounds with known activity can be performed to develop structure-activity relationships. The verrucarins as represented by verrucarin A are among the most potent cytostatic agents known and will be approached by developing a new procedure to geminal alkylation and lactone annelation. The former embodies a new concept in adjusting the oxidation level of carbon. A key feature in creating the bicyclo(3.2.1)oxanonane system is a Claisen rearrangement. Synthesis of the macrolide unit envisions a novel solution to the problem of chiral synthesis. The anthracycline family of potent antibiotic and antitumor agents is represented by pillaromycin A which is known to be less toxic than other members of this family such as daunomycin and adriamycin. The approach features a new and novel approach to protecting a phenolic ring and envisions the development of a novel and potentially very useful annelating agent via a Diels-Alder reaction, 2-methoxy-3-phenylthio-1,3-butadiene. The third part deals with the antileukemic iridoid allamandin. The strategy develops a new approach to secoalkylation, the development of stereochemistry via the rigid bicyclo(3.3.0)octane system, and novel ways to adjust the oxidation level of carbon.